P367: LONG TERM OUTCOMES OF NEWLY DIAGNOSED CRLF2 REARRANGED B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: J. Senapati, E. J. Jabbour, N. J. Short, F. Ravandi, P. Kebriaei, T. M. Kadia, G. Borthakur, N. Pemmaraju, R. S. Garris, D. Bansal, S. Konoplev, S. Wang, W. Wang, G. Tang, K. P. Patel, M. Konopleva, N. Jain
Journal: HemaSphere (2022)

Background: CRLF2 rearranged B cell acute lymphoblastic leukemia (B-ALL), a subtype of Philadelphia (Ph) -like ALL, constitutes a high-risk subset of B-ALL with poor outcomes with chemotherapy. Targeted therapies such as blinatumomab (blina) or inotuzumab (ino) may improve treatment outcomes for these patients (pts). Aims: To study the outcomes of newly diagnosed CRLF2 rearranged B-ALL treated with hyper CVAD based regimens and the impact of targeted therapies like inotuzumab and blinatumomab Methods: We retrospectively analyzed pts with newly diagnosed B-ALL (diagnosed between 01/2001 and 12/2021) at our center who had documented CRLF2 overexpression. Initial therapy, including use of ino and blina in CR1 were noted. Outcomes measures included CR/CRi, MRD response, relapse free survival (RFS) and overall survival (OS). RFS was censored at allogeneic stem cell transplantation (ASCT). Results: A total of 76 pts with a median age of 38 years (yrs) (range, 18-80) were identified, of which 70% were males and 81% were of Hispanic ethnicity. All pts had overexpression of CRLF2 documented by flow cytometry or gene expression profile. A subset of pts (n=37) had a concomitant CRLF2 FISH performed with all confirming CRLF2 rearrangement. Baseline disease parameters, treatment and outcomes are detailed in Table 1. Sixty-five pts (85%) received Hyper-CVAD based induction therapy [HCVAD-based (n=51); mini-CVD-based (n=14)] and 11 (15%) received augmented BFM. We focus on the outcomes of pts treated with HCVAD/mini-HCVD (n=65); among these pts, 24/65 (37%) received blina in CR1 during consolidation at a median of 3.6 months after starting induction therapy, 22/65 (34%) received ino in CR1 (in C1 as part of mini-HCVD-ino, n=14; in C2 as part of HCVAD, n=8). A total of 14/65 (22%) received both ino and blina in CR1; 32/65 (49%) received ino and/or blina. The median follow-up was 39 months (mos). CR/CRi rate after C1 was 52/65 (80%) with 25/47 (53%) MRD evaluable pts and 25/65 (38%) overall achieving MRD-neg post C1. The median RFS and OS was 17.6 and 26.6 mos, respectively (Fig. 1). Among the 32 pts who received ino and/or blina, the median RFS and OS was 17.6 mos and 38.8 mos respectively. CR/CRp rate after C1 among pts who received mini-HCVD-ino in C1 was 100% (14/14) with 79% MRD-neg. On landmark analysis to the time to blina initiation, blina treated pts had similar RFS and trended for improved OS. A total of 19/65 (29%) had ASCT in CR1; all were MRD-neg prior to ASCT. Landmark analysis for OS based on the time of ASCT (6 mos) in CR1 favored ASCT in CR1 (47.2 vs. 17.6 mos, p=0.04). Table 1: - Disease and treatment parameters Parameters N (%) or median [range] (N=76) Age, yrs 38 [18-80] Gender, male 53 (70) Ethnicity Hispanic 62 (81) Baseline parameters WBC (x 109/L) 17 [1-602] Platelets (x 109/L) 39 [3-195] PB blasts (%) 72 [0-98] BM blasts (%) 89 [29-98] CNS positive 10 (80) Cytogenetics and molecular Diploid karyotype 28 (37) CRLF2 mutation (n=31) 4 (13) JAK2 mutation (n=67) 25 (37) JAK1 mutation (n=31) 9 (29) Frontline regimen Augmented BFM 11 (15) HCVAD 51 (67) Chemotherapy alone 33/51 (65) with ino alone 2/51 (4) with blina alone 10/51 (20) with ino + blina 6/51 (12) Mini-HCVD-ino 14 (18) with ino alone 6 (43) with ino + blina 8 (57) Image:Summary/Conclusion: Despite improvements in treatment options, CRLF2 overexpressed B-ALL continue to have inferior outcomes. Earlier initiation of targeted therapies might improve outcomes.